The aims of this research cnter on the application of high resolution NMR methods to the study of some central problems in macromo/ecular structure, dynamics, and function. The proposal requests funding for high field spectrometer capable of applying modern ID and 2D approaches to resolve, assign and analyze the relaxation characteristics of resonances in the 1H and 31P spectra of proteins, enzyme-substrate complexes, and oligomeric DNA. Major questions to be addressed include the following. 1) How do signals in the amino acid sequence of a protein steer the folding of the protein into its native structure? A series of related, small bee venom neuropeptides will be studied. 2) What are the structural principles that act in DNA recombination events? A series of synthetic stable cruciform duplexes will be studied. 3) What kind of "breathing" motions determine protein H-exchange behavior? Can these be manipulated to label the parts of a protein directly involved in its function, and thereby measure the free energy contribution of each part? The cytochrome c redox transition, and its interaction with other proteins, will be studied. 4) In the area of 3D protein structure, evolving 2D NMR and distance geometry methods will be used to determine the structure of a growth factor protein. 5) Can NMR provide direct insight into events at the active site of an enzyme? Several enzyme kinase - substrate/product complexes will be studied.